Silanized colloidal silica preparations are used in a variety of industrial applications including, for example, production of abrasion resistant coatings, xerographic toner materials, and density gradient separation of biological materials.
Preparation of silanized colloidal silica can be difficult, since colloidal silica is inherently unstable under conditions which are optimal, if not necessary, for silanization, e.g., acidic pH. Under such acidic conditions, the silica often "gels", or loses its suspended properties to form a semi-solid jelly-like material. Under more neutral or alkaline pH conditions, the silanization does not proceed efficiently, possibly due to self-condensation of the silane. While for some applications (e.g., anti-abrasion coatings) it is not critical to retain the silica particles in a suspended state, for other applications (e.g., density gradient materials), it is important to retain the colloidal properties of the suspension.
Various methods have been devised to circumvent the recognized problems of silanization. According to one method, silanization is carried out in the presence of organic solvents in the absence of water; however, such organic solvents are difficult to remove from the preparation, and are not desirable in many applications, such as in density gradient materials, since they may be toxic or otherwise deleterious to the application.
Another known method for silanizing silica particles uses a catalyst. Again, this has the problem of adding unwanted, potentially toxic materials to the preparation. Moreover, addition of organic solvents and/or catalysts to the preparation potentially create higher levels of toxic waste, which must be disposed of in increasingly limited areas of the country. Therefore, it would be useful to have available alternate production methods that utilize water-soluble, environmentally safe reagents and intermediates.
U.S. Pat. No. 4,927,750 describes a method of preparing an organosilanized colloidal silica that is relatively non-toxic to cells; however, the method of preparation includes adding silane to the colloidal silica in a "dropwise" or gradual manner over a period of hours, while the mixture is held at a relatively high temperature (75.degree. C.). This method is time-consuming and does not readily lend itself to bulk manufacturing methods. While the method may be carried out under alkaline conditions, it is stressed that the addition of silane to the silica must be gradual. Moreover, slight deviations from the prescribed method may lead to gelling of the suspension, making it unusable for certain applications, as described above.
The present invention solves many of the problems inherent in preparations made using prior art methods, such as instability of preparations, presence of organic solvents and other toxic intermediates, and generation of toxic by-products and waste. That is, according to prior art methods, aqueous formulations could only be prepared by painstakingly slow mixing of the organosilane with the colloidal silica; otherwise, the suspension would precipitate. Alternatively, the preparation could be made using organic solvents; however, the use of such reagents is not desirable for colloidal silica compositions for certain uses, such as in preparation of biological materials. Nor is the use of such reagents particularly desirable from the standpoint of minimizing hazardous waste production.
The present invention therefore overcomes the problems inherent in prior art methods by providing a method for preparing organosilanized colloidal silica particles that allows silanization of the silica under aqueous conditions which can be easily scaled up for bulk manufacturing processes. The resulting silanized colloidal silica preparation is extremely stable and remains in the soluble phase, even after multiple cycles of autoclaving and/or gamma irradiation, as required for sterilization of the medium. The formulation is particularly well-suited for use with animal cell preparations, since it can be suspended in a physiological salt solution without gelling or precipitating. Further it is relatively non-toxic to such cells, as evidenced by the observation that it can be used to process human cells for transplantation without inducing adverse effects in recipient patients.